A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in mCRPC Patients

Phase 2RecruitingNCT06155084

Hinova Pharmaceuticals Inc.84 enrolled

Overview

The overall objective of this Phase 1 study is to evaluate the safety, PK,and anti-tumor activity of daily oral dosing with HP518,selecting the RP2D of HP518 based on assessments of patients with progressive mCRPC in dose-escalation phase

This First in Human dose escalation and expansion study of HP518 in patients with progressive mCRPC after NHA and chemotherapy is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide preliminary efficacy for the reference of future studies.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Metastatic Castration-resistant Prostate Cancer

Interventions

HP518 - Dose EscalationDRUG

Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort

HP518 - Dose EscalationDRUG

Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort

HP518 -Dose ExpansionDRUG

Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male, age ≥18 2. Patients with androgen receptor (AR) ligand binding domain (LBD) activation mutations (the dose expansion part of stage II) 3. Has histologically confirmed adenocarcinoma of the prostate, but there are no known significant neuroendocrine differentiation or small cell characteristics. 4. Has metastatic disease documented by 2 or more bone lesions by bone scan or soft tissue disease progression observed by CT/MRI at the beginning of study. 5. the progression of the disease after receiving at least one new endocrine therapy and progressing with at least first-line chemotherapy. 6. Must have recovered from toxicities related to any prior treatments 7. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy. 8. ECOG performance status score of 0 to 1. Exclusion Criteria: 1. Combination of research or commercially available drugs targeting AR 2. Has had any other anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177LuPSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518. 3. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy). 4. Has significant cardiovascular disease.

Locations (27)

Outcomes

Primary Outcomes

Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drugorally administered HP518 (Part 1)

To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)

Time frame: 28 DAYS

Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness

To evaluate the safety of orally administered HP518 (Part 1)

Time frame: Through study completion, an average of 1 year

Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

To evaluate the safety of orally administered HP518 (Part 1)

Time frame: Through study completion, an average of 1 year

Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

To evaluate the safety of orally administered HP518 (Part 1)

Time frame: Through study completion, an average of 1 year

Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

To evaluate the safety of orally administered HP518 (Part 1)

Time frame: Through study completion, an average of 1 year

PSA50 response rate

Proportion of patients showing a PSA decline by ≥50% between baseline and Week 12 of dosing with HP518.

Time frame: 12 weeks

Secondary Outcomes

Central Contacts

Qianrong Xiang

CONTACT

+86 28 8505 8465 qrxiang@hinovapharma.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

The Second Hospital Of Anhui Medical University

Hefei, Anhui, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

RECRUITING

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

RECRUITING

The Second Affiliated Hospital Of Chongqing Medical University

Chongqing, Chongqing Municipality, China

RECRUITING

The First Affiliated Hospital Of Xiamen Univeristy

Xiamen, Fujian, China

NOT_YET_RECRUITING

Lanzhou University Second Hospital

Lanzhou, Gansu, China

RECRUITING

The Third Affiliated Hospital of Southern Medical University

Guangzhou, Guangdong, China

RECRUITING

The Affiliated Hospital Of Guizhou Medical University

Guiyang, Guizhou, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

...and 17 more locations

area under the concentration-time curve (AUC)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

Maximum concentration (Cmax)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

Time to maximum concentration (Tmax)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

Apparent terminal elimination half-life (T1/2)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

oral clearance (CL/F)

Assessment of pharmacokinetic parameters of HP518

Time frame: 12 weeks

According to PCWG3

evaluate PSA50 response rate: PSA decline by≥50% between baseline and 4 weeks/8 weeks/12 weeks( only Part 1) of dosing with HP518

Time frame: 8 weeks

According to PCWG3, evaluate time to PSA progression

PCWG3 definition: PSA increase \>25% and \>2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart) nadir, confirmed by progression at 2 time points at least 3 weeks apart)

Time frame: Through study completion, an average of 1 year

Time to radiographic progression by investigator PCWG3 definition

using the RECIST v1.1 and PCWG3 definition

Time frame: Through study completion, an average of 1 year

Evaluate the modified best overall response mBOR by investigator

According to RECIST (version 1.1) and PCWG3

Time frame: Through study completion, an average of 1 year

analyze the efficacy of patients with different AR phenotypes(Part 2)

According to genetic testing results

Time frame: Through study completion, an average of 1 year